title: Inhibition of human carbonic anhydrase isoforms I-XIV with sulfonamides incorporating fluorine and 1,3,5-triazine moieties.
abstract: Reaction of cyanuryl fluoride with sulfanilamide or 4-aminoethylbenzenesulfonamide afforded triazinyl-substituted benzenesulfonamides incorporating fluorine, which were further derivatized by reaction with amines, amino alcohols, amino acids or amino acid esters. Inhibition studies of all the human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, hCA I-XIV with these compounds revealed that they show moderate-weak inhibition of hCA III, IV, VA and XIII, rather moderate inhibition against hCA I, VI, and IX, and excellent inhibition of the physiologically relevant hCA II, VII and XII. The inhibition profile of these fluorine containing triazinyl sulfonamides is thus very different from the corresponding analogs incorporating chlorine, which were previously investigated as inhibitors of some of these enzymes.
authors.affiliation: Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Ceruso
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Andrea
authors.initials: A
authors.lastname: Scozzafava
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024401:Carbonic Anhydrase I / Q000737:chemistry* / Q000378:metabolism*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005461:Fluorine / Q000737:chemistry*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D000077145:Sulfanilamide; D013424:Sulfanilamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014227:Triazines / Q000737:chemistry*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013424:Sulfanilamides; D014227:Triazines; D000077145:Sulfanilamide; D005461:Fluorine; D024401:Carbonic Anhydrase I
keywords: 1,3,5-Triazine; Carbonic anhydrase; Isoform-selective inhibitor; Sulfonamide